Systemic and Immunotoxicity Induced by Topical Application of Perfluoroheptane Sulfonic Acid (PFHpS) in a Murine Model

Details

• Personal Author:
  Anderson, Stacey E. ; Cooper MP ; Jackson LG ; Lukomska E ; Weatherly LM
• Description:
  Background and Purpose: Per- and polyfluoroalkyl substances (PFAS) comprise a broad class of synthetic surfactants used in many industrial and consumer products, from firefighting foams and stain-resistant textiles to food packaging, non-stick cookware, cosmetics, and personal care products. The hydrophobic and hydrophilic moieties of PFAS give them both oil and water-repellent properties, and their carbon-fluorine bonds make them highly stable biologically and environmentally. Due to these properties, PFAS are used widely, increasing the potential for human exposure through oral, dermal, and respiratory routes. Although multiple PFAS are detectable in human serum, research is needed to identify and characterize the potential biological effects of each PFAS and the specificity pf these effects to the exposure route. One such PFAS commonly detected in human serum is perfluoroheptane sulfonate (PFHpS). This study investigates the systemic and immune effects of dermal exposure to PFHpS in a murine model (B6C3F1, female mice). Methods: Following a 28-day sub-chronic dermal exposure to PFHpS (0.3125%, 0.625%, and 1.25% or 7.8-15.6mg/kg/day) organ weight, serum chemistry, histology, immune phenotype, and gene expression were analyzed. To further evaluate adaptive immune responses following exposure, a second study with a 10-day sub-chronic dermal exposure to PFHpS (0.625%, 1.25%, and 2.5%) was performed. Results: Supporting the relevance of dermal contact, PFHpS levels increased in serum and urine with increasing PFHpS exposure concentration. Exposed skin demonstrated epidermal thickening supported by gene expression changes associated with barrier function and wound healing. Regarding hepatic effects, PFHpS significantly increased liver weight, serum alkaline phosphatase, and serum alanine aminotransferase. Significant decreases in serum glucose and significant increases in serum cholesterol were observed. Liver histological findings included hypertrophy and immune cell infiltration. PFHpS exposure altered the expression of genes associated with steatosis, fatty acid metabolism, hepatotoxicity, lipid transport, and necrosis. Suggestive of immunotoxicity, exposure to 1.25% PFHpS for 28 days decreased spleen weight, thymus weight, and spleen cellularity. By histology, the spleens of PFHpS-treated mice were thinner and had smaller lymphoid aggregates. The IgM response to sheep red blood cells was significantly reduced following the 10-day exposure to 1.25% and 2.5% PFHpS. Immune phenotyping of the spleen identified that PFHpS altered immune cell subtype abundance, including CD11+ myeloid-derived cells, CD4 T cells, and B cell numbers. Conclusions: These findings suggest that dermal PFHpS exposure results in hepatotoxicity and altered immune function. However, further work is necessary to characterize the mechanisms of these alterations and their relevance to human health outcomes. [Description provided by NIOSH]
• Subjects:
  Immune System Laboratories Liver Occupational Health Safety Skin Surface-Active Agents
• Keywords:
  Dermal Exposures Hepatotoxicity Immune Reaction Laboratory Animals Liver Damage Per- And Polyfluoroalkyl Substances PFAS Surfactants
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  198
• NIOSHTIC Number:
  nn:20069323
• Citation:
  Toxicologist 2024 Mar; 198(S1):269
• CAS Registry Number:
  Perfluoroheptanesulfonic acid (CAS RN 375-92-8)
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Manufacturing ; Public Safety
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 63rd Annual Meeting & ToxExpo, March 10-14, 2024, Salt Lake City, Utah
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6fd4ae4aceca2ff6d5d46322de62d2e0918780e902225598985d67c80b0aac0d94213a4df2363f80fea91c08e5aa1dc486139df42af06a0310326c3d6eab43f3
• Download URL:
  https://stacks.cdc.gov/view/cdc/207823/cdc_207823_DS1.pdf
• File Type:
  [PDF - 539.92 KB ]